Twardy Shannon M, Hanson Sarah M, Jursa Thomas, Gaitens Joanna M, Kalinich John M, McDiarmid Melissa A, Smith Don R
Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, CA, USA.
Division of Occupational and Environmental Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Environ Toxicol Pharmacol. 2023 Nov;104:104283. doi: 10.1016/j.etap.2023.104283. Epub 2023 Sep 27.
Retained lead fragments from nonfatal firearm injuries pose a risk of lead poisoning. While chelation is well-established as a lead poisoning treatment, it remains unclear whether chelation mobilizes lead from embedded lead fragments. Here, we tested whether 1) DMSA/succimer or CaNaEDTA increases mobilization of lead from fragments in vitro, and 2) succimer is efficacious in chelating fragment lead in vivo, using stable lead isotope tracer methods in a rodent model of embedded fragments. DMSA was > 10-times more effective than CaNaEDTA in mobilizing fragment lead in vitro. In the rodent model, succimer chelation on day 1 produced the greatest blood lead reductions, and fragment lead was not mobilized into blood. However, with continued chelation and over 3-weeks post-chelation, blood lead levels rebounded with mobilization of lead from the fragments. These findings suggest prolonged chelation will increase fragment lead mobilization post-chelation, supporting the need for long-term surveillance in patients with retained fragments.
非致命性火器伤残留的铅碎片存在铅中毒风险。虽然螯合疗法作为铅中毒的治疗方法已得到广泛认可,但尚不清楚螯合疗法能否促使嵌入的铅碎片中的铅被动员出来。在此,我们使用稳定铅同位素示踪方法,在嵌入碎片的啮齿动物模型中测试了:1)二巯丁二酸/丁二酸或依地酸钙钠是否能在体外增加碎片中铅的动员;2)丁二酸在体内对碎片中的铅进行螯合是否有效。在体外动员碎片中的铅方面,二巯丁二酸比依地酸钙钠有效10倍以上。在啮齿动物模型中,第1天进行丁二酸螯合使血铅降低幅度最大,且碎片中的铅未被动员到血液中。然而,随着螯合的持续以及螯合后3周以上,血铅水平随着碎片中铅的动员而反弹。这些发现表明,延长螯合时间会增加螯合后碎片中铅的动员,这支持了对有残留碎片的患者进行长期监测的必要性。